Cells mediate innate immunity through direct cell lysis by intracytoplasmic azurophilic granules; and modulation of other immune cells by release of proinflammatory cytokines; such as interferon (IFN)-ɣ and tumor necrosis factor (TNF). The effector function of NK cells is regulatingf by the balance; between activating and inhibitory receptor signals.
In contrast, NK cell inhibition is regulating by killer cell; immunoglobulin like receptors (KIRs) and CD94/NKG2A; which recognize major histocompatibility complex (MHC) class I molecules on target cells. Therefore, MHC class I-deficient cancer or transforming cells are highly sensitive to NK cells. Because of these inherent functions of NK cells, they have attracted attention as promising immunotherapeutics for cancer and viral infections.
But by using cell therapy to eliminate tumors from cancer patients. From an immunotherapeutic approach; NK cells are considering to be a promising effector immune cell type for new cancer therapy. Although many kinds of autologous and allogeneic NK cells have been known to mediate antigen-independent tumor cytotoxicity activity.
But the therapeutic potential of NK cell-based immunotherapy is still unclear. PBMCs have been using as one of the sources of NK cells for clinical applications. The use of feeder cells has been an essential method for securing many cells that can have a therapeutic effect. However, the use of feeder cells might induce the problem of infectious disease and the regulatory hurdles in the manufacturing pharmaceutical products, although it had an advantageous for NK cell expansion.
Human NK cell expansion requires multiple signals for survival, proliferation, and activation. Human NK cell cultures traditionally are maintained for 14 to 28 days and require frequent manipulations, such as media changes, to refresh cytokines and other growth factors and cell splitting to ensure that NK cells are maintained at a concentration that optimizes their growth and viability.
The study finding that NK cells stimulated with IL-15/IL-18/IL-27 showing the highest cytotoxic activity compared to those stimulated with IL-15/IL-18, IL-2 alone, or IL-15 alone, and this effect was accompanied by increased intracytoplasmic perforin granule accumulation. In study data suggest that IL-27 acted synergistically with IL-15 and that IL-18 contributes to NK cell cytotoxic activation by increasing cytolytic granule, perforin, and granzyme accumulation